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Publication . Article . 2005

Effects of virion surface gp120 density on infection by HIV-1 and viral production by infected cells

Estanislao Bachrach; Hanna Dreja; Yea-Lih Lin; Clément Mettling; Valérie Pinet; Pierre Corbeau; Marc Piechaczyk;
Open Access  
Published: 01 Feb 2005 Journal: Virology, volume 332, pages 418-429 (issn: 0042-6822, Copyright policy )
Publisher: Elsevier BV
Country: France
Abstract The quantity of envelope glycoprotein molecules (Env) on HIV-1 particles is still an issue of debate and, depending on the strain of virus and the nature of the producer cells, it can vary greatly. Here, we have attempted to address how Env density influences HIV-1 fitness. To this aim, we have produced HIV-1-derived viral particles with various amounts of R5 Env (low Env: Envlo; high Env: Envhi), using a regulatable expression system. The infectivity was assayed on human cells, engineered to express the HIV receptor CD4 and the co-receptor CCR5, as well as on peripheral blood lymphocytes and macrophages. In these experiments, low levels of Env were sufficient for cell infection, albeit at low efficiency. Increasing the amount of Env resulted in cooperatively improved infectivity, but a threshold was rapidly attained, indicating that only a fraction of Env was required for efficient infection. Unexpectedly, Env incorporation beyond what gives maximal infection transiently stimulated the expression of proviral genes, as well as retrovirus production, in newly infected cells. This was likely a consequence of induced NF-κB activity, as this transcription factor is triggered by Envhi, but not by Envlo, virions. Thus, our data suggest that one major effect of high Env density on the surface of HIV may not be better infection yields but rather improved viral production by newly infected cells.
Subjects by Vocabulary

Microsoft Academic Graph classification: Virology Biology Transcription factor Infectivity Cell medicine.anatomical_structure medicine NF-κB chemistry.chemical_compound chemistry Retrovirus biology.organism_classification Glycoprotein chemistry.chemical_classification Virus Gene

Medical Subject Headings: viruses virus diseases


Virology, Cultured Virion/immunology/*physiology, Cell Line HIV Envelope Protein gp120/*physiology HIV Infections/*virology HIV-1/*pathogenicity/*physiology Humans Luciferases/genetics/metabolism Transfection Tumor Cells, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, HIV-1, Env, Envelope glycoprotein, Infection, LTR activation, NF-κB

58 references, page 1 of 6

Arganaraz, E.R., Schindler, M., Kirchhoff, F., Cortes, M.J., Lama, J., 2003. Enhanced CD4 down-modulation by late stage HIV-1 nef alleles is associated with increased Env incorporation and viral replication. J. Biol. Chem. 278 (36), 33912 - 33919.

Bachrach, E., Marin, M., Pelegrin, M., Karavanas, G., Piechaczyk, M., 2000. Efficient cell infection by Moloney murine leukemia virusderived particles requires minimal amounts of envelope glycoprotein. J. Virol. 74 (18), 8480 - 8486. [OpenAIRE]

Baribaud, F., Doms, R.W., 2001. The impact of chemokine receptor conformational heterogeneity on HIV infection. Cell. Mol. Biol. (Noisy-le-Grand) 47 (4), 653 - 660.

Baron, U., Bujard, H., 2000. Tet repressor-based system for regulated gene expression in eukaryotic cells: principles and advances. Methods Enzymol. 327, 401 - 421. [OpenAIRE]

Berger, E.A., Murphy, P.M., Farber, J.M., 1999. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu. Rev Immunol. 17, 657 - 700.

Blaak, H., van't Wout, A.B., Brouwer, M., Hooibrink, B., Hovenkamp, E., Schuitemaker, H., 2000. In vivo HIV-1 infection of CD45RA(+)CD4(+) T cells is established primarily by syncytium-inducing variants and correlates with the rate of CD4(+) T cell decline. Proc. Natl. Acad. Sci. U.S.A. 97 (3), 1269 - 1274.

Briggs, J.A., Simon, M.N., Gross, I., Krausslich, H.G., Fuller, S.D., Vogt, V.M., Johnson, M.C., 2004. The stoichiometry of Gag protein in HIV-1. Nat. Struct. Mol. Biol. 11 (7), 672 - 675.

Chertova, E., Bess Jr., J.W., Crise, B.J., Sowder, I.R., Schaden, T.M., Hilburn, J.M., Hoxie, J.A., Benveniste, R.E., Lifson, J.D., Henderson, L.E., Arthur, L.O., 2002. Envelope glycoprotein incorporation, not shedding of surface envelope glycoprotein (gp120/SU), Is the primary determinant of SU content of purified human immunodeficiency virus type 1 and simian immunodeficiency virus. J. Virol. 76 (11), 5315 - 5325. [OpenAIRE]

Cho, M.W., Shibata, R., Martin, M.A., 1996. Infection of chimpanzee peripheral blood mononuclear cells by human immunodeficiency virus type 1 requires cooperative interaction between multiple variable regions of gp120. J. Virol. 70 (10), 7318 - 7321.

Cohen, O.J., Kinter, A., Fauci, A.S., 1997. Host factors in the pathogenesis of HIV disease. Immunol. Rev. 159, 31 - 48.